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Cytoplasmic short linear motifs in ACE2 and integrin β3 link SARS-CoV-2 host cell receptors to endocytosis and autophagy

View ORCID ProfileJohanna Kliche, View ORCID ProfileMuhammad Ali, View ORCID ProfileYlva Ivarsson
doi: https://doi.org/10.1101/2020.10.06.327742
Johanna Kliche
1Department of Chemistry, BMC, Uppsala University, Husargatan 3, 751 23 Uppsala, Sweden
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Muhammad Ali
1Department of Chemistry, BMC, Uppsala University, Husargatan 3, 751 23 Uppsala, Sweden
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Ylva Ivarsson
1Department of Chemistry, BMC, Uppsala University, Husargatan 3, 751 23 Uppsala, Sweden
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  • For correspondence: ylva.ivarsson@kemi.uu.se
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Abstract

The spike protein of the SARS-CoV-2 interacts with angiotensin converting enzyme 2 (ACE2) and enters the host cell by receptor-mediated endocytosis. Concomitantly, evidence is pointing to the involvement of additional host cell receptors, such as integrins. The cytoplasmic tails of ACE2 and integrin β3 contain a plethora of predicted binding motifs. Here, we confirm the functionality of some of these motifs through affinity measurements. The class I PDZ binding motif in the ACE2 cytoplasmic tail binds the first PDZ domain of the scaffold protein NHERF3. The clathrin-adaptor subunit AP2 μ2 interacts with an endocytic motif in the ACE2 with low affinity and the interaction is abolished by phosphorylation of Tyr781. Furthermore, the C-terminal region of integrin b3 contains a LC3-interacting region, and its interaction with ATG8 domains is enhanced by phosphorylation. Together, our data provides possible molecular links between host cell receptors and endocytosis and autophagy.

One sentence summary Affinity measurements confirmed binding of short linear motifs in the cytoplasmic tails of ACE2 and integrin β3, thereby linking the receptors to endocytosis and autophagy.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC 4.0 International license.
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Posted October 06, 2020.
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Cytoplasmic short linear motifs in ACE2 and integrin β3 link SARS-CoV-2 host cell receptors to endocytosis and autophagy
Johanna Kliche, Muhammad Ali, Ylva Ivarsson
bioRxiv 2020.10.06.327742; doi: https://doi.org/10.1101/2020.10.06.327742
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Cytoplasmic short linear motifs in ACE2 and integrin β3 link SARS-CoV-2 host cell receptors to endocytosis and autophagy
Johanna Kliche, Muhammad Ali, Ylva Ivarsson
bioRxiv 2020.10.06.327742; doi: https://doi.org/10.1101/2020.10.06.327742

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